Sickle Cell Anemia is a disease which affects over 70,000 people in the United States of America and is the result of a point mutation in a single amino acid of hemoglobin. The mutated hemoglobin is referred to as Hemoglobin S (HbS). When HbS binds oxygen in a red blood cell, it precipitates, forming crystals that damage membranes in red blood cells, causing the red blood cells to lyse, releasing HbS into plasma, and lowering red blood cell levels (anemia). In severe cases in which this hemolysis results in a crisis of low oxygen tension, death can be the end point. It has been found that the binding of the vasorelaxant hormone, nitric oxide (NO), by HbS after it is released from red blood cells is 1000 times more efficient than the binding by normal Hb, lowering levels of “free” NO to a point at which severe vaso-constriction occurs. The lowered blood flow to tissues is thought to be a primary cause of severe bouts of pain in patients.
It is believed that released HbS is normally metabolized (catabolized) by ‘intravascular’ hemolysis processes. This process is different than ‘extra vascular’ hemolysis occurring during neonatal jaundice in which the abnormal red blood cells are recognized by RES cells and phagocytosed, ‘before’ Hb is released within the phagocyte and then heme is released prior to reaction with heme oxygenase, releasing (CO). The intravascular hemolysis processes include the binding of Hb to plasma proteins (“haptoglobins”), and the complex of Hb/haptoglobin is carried to the RES where heme is released to generate (CO). During intravascular hemolysis, some heme can be released in plasma and the free heme is bound by another protein (hemopexin), which carries the heme to the liver, where liver heme oxygenase generates the (CO).
It would be advantageous to identify (CO) measurements (e.g. via hemolysis screener) as a sensitive indicator of an abnormal level of hemolysis (intravascular and/or extra vascular) before the plasma levels of HbS reach a point at which enough NO is bound to cause vasocontrictive-dependent pain or more severe pathologies, such as a stroke, which can lead to death. This would permit Sickle Cell Anemia patients to be regularly screened for (CO) in an emergency room, hospital bedside, doctors' office, or home, etc. The urgency of action in response to high (CO) levels might vary from more intense monitoring of patients, to increasing treatment (e.g. with (NO)), to more intensive critical care.
Currently, a common clinical practice to help persons with sickle-cell anemia is a blood transfusion, often performed on a monthly basis. However, the timing of these transfusions is often solely based on the timing of the last transfusion, and not based on a clinical predictor of pain. The transfusions themselves are a source of trauma and pain to the patient, and are often very costly. Even if all these other disadvantages are addressed, often transfusions are not possible because blood is not available.
Thus, it is highly desirable to minimize the necessity of transfusions, by the detection of predictors, such as carbon monoxide (CO), from sickle-cell anemia related pathologies, such as hemolysis, that eventually lead to negative clinical effects, such as pain, anemia and increased risk of stroke, infection and deafness.
Accordingly, there is a need for an accurate and reliable method for predicting the onset of pain and/or the onset of a stroke in a human patient based on non-invasive measurements of blood gases or exhaled breath gases such as (CO).